The technique of in vivo depletion with T cell subset-specific monoclonal antibodies was used to study the involvement of CD8+ T cells in protection/pathogenesis during the acute and chronic demyelinating phases of Theiler’s murine encephalomyelitis virus (TMEV)-induced disease. Mice rendered CD8-deficient prior to infection with TMEV were less efficient at clearing virus from the central nervous system compared to intact animals and also suffered demyelinating disease of earlier onset and increased severity. This indicates that CD8+ cells have a protective role in virus clearance at early times post-infection, and may also be involved in downregulating the severity of the chronic demyelinating disease. How CD8+ T cells function to produce these effects is discussed.
AubertC.,
ChamorrowM.,
BrahicM.1987; Identification of Theiler’s virus infected cells in the central nervous system of the mouse during demyelinating disease. Microbial Pathogenesis 3:319–326
BlakemoreW. F.,
WelshC. J. R.,
TonksP.,
NashA. A.1988; Observations on demyelinating lesions induced by Theiler’s virus in CBA mice. Acta neuropathologica 76:581–589
ClatchR. J.,
MelvoldR. W.,
MillerS. D.,
LiptonH. L.1985; Theiler’s murine encephalomyelitis virus-induced demyelinating disease in mice is influenced by the H.2D regions: correlation with TMEV-specific delayed-type hypersensitivity. Journal of Immunology 135:1408–1414
ClatchR. J.,
MelvoldR. W.,
Dal CantoM. C.,
MillerS. D.,
LiptonH. L.1987b; The Theiler’s murine encephalomyelitis virus (TMEV) model for multiple sclerosis shows a strong influence of the murine equivalents of HLA-A, B and C. Journal of Neuroimmunology 15:121–135
CobboldS. P.,
JayasuriyaA.,
NashA. A.,
ProsperoT. D.,
WaldmannH.1984; Therapy with monoclonal antibodies by elimination of T cell subsets in vivo. Nature, London 312:548–551
FriedmannA.,
FrankelG.,
LorchY.,
SteinmanL.1987; Monoclonal anti-I-A antibody reverses chronic paralysis and demyelination in Theiler’s virus-infected mice: critical importance of time of treatment. Journal of Virology 61:898–903
LindsleyM. D.,
ThiemannR.,
RodriguezM.1991; Cytotoxic T cells isolated from the central nervous systems of mice infected with Theiler’s virus. Journal of Virology 65:6612–6620
LiptonH. L.,
MelvoldR.1984; Genetic analysis of susceptibility to Theiler’s virus-induced demyelinating disease in mice. Journal of Immunology 132:1821–1825
NashA. A.,
JayasuriyaA.,
PhelanJ.,
CobboldS. P.,
WaldmannH.,
ProsperoT.1987; Different roles for L3T4+ and Lyt 2+ T cell subsets in the control of an acute herpes simplex virus infection of the skin and nervous system. Journal of General Virology 68:825–833
RodriguezM.,
LafuseW. P.,
LeibowitzJ.,
DavidC. S.1986a; Partial suppression of Theiler’s virus-induced demyelination in vivo by administration of monoclonal antibodies to immune-response gene products (la antigens). Neurology 36:964–970
RodriguezM.,
LeibowitzJ.,
DavidC. S.1986b; Susceptibility to Theiler’s virus-induced demyelination. Mapping of the gene within the H-2D region. Journal of Experimental Medicine 163:620–631
RoosR. P.,
FirestoneS.,
WollmanR.,
VariakojisD.,
ArnasonB. G. W.1982; The effect of short-term and chronic immunesuppression on Theiler’s virus demyelination. Journal of Neuroimmunology 2:223–234
SriramS.,
CarollL.,
FortinS.,
CooperS.,
RangesG.1988; In vivo immunomodulation by monoclonal anti-CD4 antibody. II. Effect on T cell response to myelin basic protein and experimental allergic encephalomyelitis. Journal of Immunology 141:464–468
WelshC. J. R.,
TonksP.,
NashA. A.,
BlakemoreW. F.1987; The effect of L3T4 T cell depletion on the pathogenesis of Theiler’s murine encephalomyelitis virus infection in CBA mice. Journal of General Virology 68:1659–1667